This grant proposal, "MRI Measurement of Relative CMRO2: Validation using PET", is an application for an R01 award. The goal of the proposed project is to 1) develop and validate MR methods for quantitative imaging of the relative regional cerebral metabolic rate of oxygen utilization (rCMRO2) under different physiological conditions in animal models and in human volunteers, and 2) validate the relationship between changes in CMRO2 and hemodynamics in the setting of neuronally-modulated focal brain activation. The fundamental hypothesis is that MR measurements of multiple hemodynamic observables - BOLD signal, CBF, and CBV - will enable regional and temporal assessment of relative CMRO2 in agreement with positron emission tomography in rodents and humans. These studies will further test a scientific hypothesis of cerebral physiology: that changes in CMRO2 and CBF exhibit a coupling relationship in general accordance with diffusion-limited models of oxygen delivery from the blood to brain tissue, and as demonstrated by preliminary data. Within this framework we will test the basic assumptions about the relationship between MRI signals and the underlying physics and physiology and provide corroborative data for MR1 measurements of relative CMRO2 and CBF. Successful completion of the proposed studies will establish, a new tool for assessment of cerebral functional physiology and preface the application of these techniques to cerebral pathology.